Nature Medicine Contents: September 2017 Volume 23 Number 9 pp 1005-1111

If you are unable to see the message below, click here to view.

TABLE OF CONTENTS September 2017 Volume 23, Issue 9 Editorial News Correction News and Views Review Perspective Articles Letters Analysis Resource Advertisement Nature Index 2017: Innovation  The Nature Index Innovation supplement examines the link between high-quality research and the commercialization of products and services, with particular focus on scientific discoveries and its economic potential. Read the full supplement free for six months Subscribe   Facebook   RSS   Recommend to library   Twitter   Advertisement Animation: Amyotrophic lateral sclerosis   Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder that primarily affects the motor system, resulting in progressive muscle weakness, which ultimately becomes fatal. This animation focuses on the mechanisms that drive ALS pathogenesis.   Watch the Animation free online >> Funded by a grant from MT Pharma America, Inc.   Advertisement Scientific rigour and reproducibility  Science progresses by standing on the shoulders of giants, to paraphrase Newton. But what if those shoulders aren't steady? Read about how to assess and improve the reliability of biomedical research.  Access this Collection of articles free online Produced with support from:  Gilson & sciNote   Advertisement Free Naturejobs Career Expo London - registration is now open  The 11th annual Naturejobs Career Expo will be held in London on October 4, 2017. Join us for your chance to network with leading global employers, receive one-to-one CV checking, attend free talks and workshops, learn how to enhance your employability and lots more.  Register FREE today!    Editorial Top Children first   p1005 doi:10.1038/nm.4404 Drugs administered to children with cancer were typically developed under the assumption that childhood cancers are similar to their tissue-matched adult counterparts. Focusing on identifying and targeting alterations present specifically in childhood tumors will accelerate the development of tailored therapies and improve the prognosis of children with cancer. News Top Uncovering cancer: How enlisting T cells can boost the power of immunotherapy   pp1006 - 1008 Amanda B. Keener doi:10.1038/nm0917-1006 Inflammatory illness: Why the next wave of antidepressants may target the immune system   pp1009 - 1011 Nicole Wetsman doi:10.1038/nm0917-1009 Correction Top Correction   p1011 doi:10.1038/nm0917-1011 News and Views Top The enteric virome in hematopoietic stem cell transplantation: ready for its close-up   pp1012 - 1013 Shuichiro Takashima and Alan M Hanash doi:10.1038/nm.4403 A new study highlights dynamic changes in the enteric virome after hematopoietic stem cell transplantation in humans, pointing to a correlation between these changes and graft-versus-host disease. See also: Letter by Legoff et al. SPOP tips the balance of BETs in cancer   pp1014 - 1015 Katie A Fennell and Mark A Dawson doi:10.1038/nm.4398 Cancer-associated mutations in speckle-type POZ (pox virus and zinc-finger) protein confer neomorphic activity, altering its substrate affinities and its response to bromodomain and extraterminal inhibitors in prostate and endometrial cancer. See also: Article by Janouskova et al. | Letter by Zhang et al. | Letter by Dai et al. Sex-specific disease-associated modules for depression   pp1015 - 1017 Ronald S Duman doi:10.1038/nm.4391 A recent study reveals sexually dimorphic disease-associated gene-expression modules and hub genes in postmortem brains from female and male individuals with depression. These modules are conserved in mouse models of depression. See also: Resource by Labonte et al. Nature Medicine JOBS of the week Postdoctoral Fellow, School of Veterinary Medicine University of Pennsylvania Principal Investigator in Human Physiology and Experimental Medicine University of Cambridge Post-doctoral fellow in Pulmonary Research at University of Maryland School of Medicine University of Maryland School of Medicine PhD programs of the Faculty of Medicine Geneva University of Geneva, Faculty of Medicine Associate Director, Joint Center For Cancer Precision Medicine (CCPM) Dana-Farber Cancer Institute (DFCI) More Science jobs from Nature Medicine EVENT 27th Annual Mayo Clinic Symposium on Sports Medicine 2017 10.11.17 Rochester, USA More science events from Review Top Microglia emerge as central players in brain disease   pp1018 - 1027 Michael W Salter and Beth Stevens doi:10.1038/nm.4397 In this Review, Salter and Stevens discuss the role of microglia in CNS disorders such as autism, neurodegenerative disorders, Alzheimer's disease, and chronic pain. Perspective Top Functional precision cancer medicine—moving beyond pure genomics   pp1028 - 1035 Anthony Letai doi:10.1038/nm.4389 Anthony Letai proposes wider adoption of functional assays in efforts to match the right drug to the right patient and discusses why these assays might be complementary to existing genomics-based approaches. Advertisement Nature Outline: Corneal repair The eye is a remarkable organ that requires total clarity. This Outline introduces the stem cells that regenerate the surface of the cornea — and what happens when we lose them.  Access free online Produced with support from  Translational Research Informatics Center (TRI)  Kyoto Prefectural University of Medicine   Articles Top D-mannose induces regulatory T cells and suppresses immunopathology   pp1036 - 1045 Dunfang Zhang, Cheryl Chia, Xue Jiao, Wenwen Jin, Shimpei Kasagi et al. doi:10.1038/nm.4375 D-mannose promotes Treg cell differentiation and is therapeutic in mouse models of autoimmune diabetes and airway inflammation. Opposing effects of cancer-type-specific SPOP mutants on BET protein degradation and sensitivity to BET inhibitors   pp1046 - 1054 Hana Janouskova, Geniver El Tekle, Elisa Bellini, Namrata D Udeshi, Anna Rinaldi et al. doi:10.1038/nm.4372 Different mutations found in endometrial and prostate tumors affecting the substrate-recognition domain of SPOP, a component of the E3 ubiquitin ligase complex, result in opposing degradation activity of BET proteins and response to BET inhibitors. This work, along with findings by Zhang et al. and Dai et al., highlights the divergent effects of recurrent mutations affecting different residues within the same functional domain of SPOP and provides scientific rationale to guide the administration of BET inhibitors in endometrial and prostate cancer patients harboring SPOP mutations. See also: News and Views by Fennell & Dawson | Letter by Zhang et al. | Letter by Dai et al. Advertisement Nature Outlook: University Spin-offs  This Outlook presents a portrait of 22 science-based start-up ventures that have emerged from universities around the world to turn laboratory research into practical, profitable products.  Access the Outlook free online for six months.    Letters Top Intrinsic BET inhibitor resistance in SPOP-mutated prostate cancer is mediated by BET protein stabilization and AKT-mTORC1 activation   pp1055 - 1062 Pingzhao Zhang, Dejie Wang, Yu Zhao, Shancheng Ren, Kun Gao et al. doi:10.1038/nm.4379 Mutations in SPOP, the gene encoding a component of the E3 ubiquitin ligase complex, impair ubiquitination-dependent degradation of BRD2, BRD3 and BRD4 proteins and result in activation of ATK-mTORC1 signaling and resistance to BET inhibitors. Pharmacological blockade of AKT represents a viable strategy to restore the sensitivity of SPOP-mutant prostate tumors to BET inhibitors. These results, together with findings by Dai et al. and Janouskova et al., uncover a new nongenetic mechanism of resistance to BET inhibition involving cancer-type-specific mutations in SPOP, and support the evaluation of SPOP mutation status to inform the administration of BET inhibitors in the clinic. See also: News and Views by Fennell & Dawson | Article by Janouskova et al. | Letter by Dai et al. Prostate cancer-associated SPOP mutations confer resistance to BET inhibitors through stabilization of BRD4   pp1063 - 1071 Xiangpeng Dai, Wenjian Gan, Xiaoning Li, Shangqian Wang, Wei Zhang et al. doi:10.1038/nm.4378 Recurrent mutations in SPOP-encoding a Cullin 3-based E3 ubiquitin ligase- in prostate cancer disrupt the recognition and degradation of ubiquitination substrates, including BET proteins. Consequently, stability of BET proteins is enhanced and this increases the resistance to BET inhibitors in SPOP-mutant prostate tumors. These results, together with those in Janouskova et al. and Zhang et al., uncover a novel non genetic mechanism of resistance to BET inhibition involving cancer type-specific mutations in SPOP, and support the evaluation of SPOP mutations to inform the administration of BET inhibitors in the clinic. See also: News and Views by Fennell & Dawson | Article by Janouskova et al. | Letter by Zhang et al. Targeting cellular senescence prevents age-related bone loss in mice   pp1072 - 1079 Joshua N Farr, Ming Xu, Megan M Weivoda, David G Monroe, Daniel G Fraser et al. doi:10.1038/nm.4385 Genetic or pharmacological depletion of senescent cells or inhibition of their function reduces bone loss in aged mice. The eukaryotic gut virome in hematopoietic stem cell transplantation: new clues in enteric graft-versus-host disease   pp1080 - 1085 Jerome Legoff, Matthieu Resche-Rigon, Jerome Bouquet, Marie Robin, Samia N Naccache et al. doi:10.1038/nm.4380 Charles Chiu and colleagues analyze the gut viromes of recipients of hematopoietic stem cell transplantation and identify characteristics associated with the severity of graft-versus-host disease in the gut. See also: News and Views by Takashima & Hanash A human APOC3 missense variant and monoclonal antibody accelerate apoC-III clearance and lower triglyceride-rich lipoprotein levels   pp1086 - 1094 Sumeet A Khetarpal, Xuemei Zeng, John S Millar, Cecilia Vitali, Amritha Varshini Hanasoge Somasundara et al. doi:10.1038/nm.4390 On the basis of new mechanistic studies of a mutant form of the apolipoprotein apoC-III that protects against coronary heart disease, Khetarpal et al. have developed therapeutic apoC-III-targeting monoclonal antibodies that lower circulating apoC-III protein and triglyceride levels in mice. Analysis Top Implications of human genetic variation in CRISPR-based therapeutic genome editing   pp1095 - 1101 David A Scott and Feng Zhang doi:10.1038/nm.4377 Analysis of the ExAC and 1000 Genomes data sets estimates the impact of inter-individual variation on the efficacy and safety of therapies based on CRISPR endonucleases. Resource Top Sex-specific transcriptional signatures in human depression   pp1102 - 1111 Benoit Labonte, Olivia Engmann, Immanuel Purushothaman, Caroline Menard, Junshi Wang et al. doi:10.1038/nm.4386 Brain-region-specific RNA-seq from humans with major depressive disorder reveals unique transcriptomic profiles in males and females, with little overlap. See also: News and Views by Duman Top Advertisement HIV IMMUNITY AND ERADICATION, A HERRENHAUSEN SYMPOSIUM November 2-3, 2017 | Hanover, Germany REGISTER NOW!   Natureevents is a fully searchable, multi-disciplinary database designed to maximise exposure for events organisers. The contents of the Natureevents Directory are now live. The digital version is available here. Find the latest scientific conferences, courses, meetings and symposia on natureevents.com. For event advertising opportunities across the Nature Publishing Group portfolio please contact natureevents@nature.com More Nature Events

You have been sent this Table of Contents Alert because you have opted in to receive it. You can change or discontinue your e-mail alerts at any time, by modifying your preferences on your nature.com account at: www.nature.com/myaccount (You will need to log in to be recognised as a nature.com registrant) For further technical assistance, please contact our registration department For print subscription enquiries, please contact our subscription department For other enquiries, please contact our customer feedback department Springer Nature | One New York Plaza, Suite 4500 | New York | NY 10004-1562 | USA Springer Nature's worldwide offices: London - Paris - Munich - New Delhi - Tokyo - Melbourne San Diego - San Francisco - Washington - New York - Boston Macmillan Publishers Limited is a company incorporated in England and Wales under company number 785998 and whose registered office is located at The Campus, 4 Crinan Street, London, N1 9XW. © 2017 Macmillan Publishers Limited, part of Springer Nature. All Rights Reserved.